JP6895464B2 - アルドース還元酵素阻害剤およびその使用方法 - Google Patents
アルドース還元酵素阻害剤およびその使用方法 Download PDFInfo
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- JP6895464B2 JP6895464B2 JP2018567299A JP2018567299A JP6895464B2 JP 6895464 B2 JP6895464 B2 JP 6895464B2 JP 2018567299 A JP2018567299 A JP 2018567299A JP 2018567299 A JP2018567299 A JP 2018567299A JP 6895464 B2 JP6895464 B2 JP 6895464B2
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- Prior art keywords
- compound
- hydrogen
- alkyl
- pharmaceutically acceptable
- halogen
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- 239000003288 aldose reductase inhibitor Substances 0.000 title description 15
- 229940118148 Aldose reductase inhibitor Drugs 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 302
- 229910052739 hydrogen Inorganic materials 0.000 claims description 186
- 239000001257 hydrogen Substances 0.000 claims description 186
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 111
- 229910052736 halogen Inorganic materials 0.000 claims description 84
- 150000002367 halogens Chemical class 0.000 claims description 84
- 150000003839 salts Chemical class 0.000 claims description 79
- 150000002431 hydrogen Chemical class 0.000 claims description 75
- 239000012453 solvate Substances 0.000 claims description 65
- 125000001188 haloalkyl group Chemical group 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 54
- -1 tetrafluoroborate Chemical compound 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 48
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
- 208000035475 disorder Diseases 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 29
- 239000003937 drug carrier Substances 0.000 claims description 24
- 108010053754 Aldehyde reductase Proteins 0.000 claims description 22
- 239000011734 sodium Substances 0.000 claims description 18
- 125000002252 acyl group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 206010012601 diabetes mellitus Diseases 0.000 claims description 17
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 17
- 125000004995 haloalkylthio group Chemical group 0.000 claims description 17
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 12
- 239000011591 potassium Substances 0.000 claims description 12
- 229910052700 potassium Inorganic materials 0.000 claims description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 9
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- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000011575 calcium Substances 0.000 claims description 9
- 229910052791 calcium Inorganic materials 0.000 claims description 9
- 229910052744 lithium Inorganic materials 0.000 claims description 9
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 8
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- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
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- 102000016912 Aldehyde Reductase Human genes 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 238000011282 treatment Methods 0.000 description 25
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- 102100027265 Aldo-keto reductase family 1 member B1 Human genes 0.000 description 21
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
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- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 11
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 11
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 11
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- 235000011054 acetic acid Nutrition 0.000 description 10
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
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- 150000007513 acids Chemical class 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 8
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4986—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with sulfur as the only hetero atom
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2021130719A (ja) * | 2016-06-21 | 2021-09-09 | ザ トラスティーズ オブ コロンビア ユニバーシティー イン ザ シティー オブ ニューヨーク | アルドース還元酵素阻害剤およびその使用方法 |
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| US8916563B2 (en) | 2010-07-16 | 2014-12-23 | The Trustees Of Columbia University In The City Of New York | Aldose reductase inhibitors and uses thereof |
| MX2020001057A (es) * | 2017-07-28 | 2020-11-24 | Applied Therapeutics Inc | Composiciones y metodos para tratar la galactosemia. |
| WO2020167937A1 (en) * | 2019-02-12 | 2020-08-20 | Applied Therapeutics, Inc. | Methods for treating cutaneous aging |
| EP3947391A1 (en) | 2019-04-01 | 2022-02-09 | Applied Therapeutics Inc. | Inhibitors of aldose reductase |
| CN114667139A (zh) * | 2019-10-08 | 2022-06-24 | 应用治疗公司 | 用于治疗磷酸甘露变位酶2缺乏的醛糖还原酶抑制剂 |
| WO2021202523A1 (en) | 2020-03-31 | 2021-10-07 | Applied Therapeutics, Inc. | Aldose reductase inhibitors for the treatment of acute respiratory distress syndrome, acute lung inflammation/injury, cardiac injury and anti-viral therapy |
| BR112022021845A2 (pt) | 2020-05-01 | 2022-12-20 | Applied Therapeutics Inc | Inibidores de aldose redutase para tratar deficiência em sorbitol desidrogenase |
| GB2619898A (en) * | 2021-03-18 | 2023-12-20 | Mylari Banavara | Combination of aldose reductase inhibitors and probenecid for the treatment of diabetic complications |
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| US8916563B2 (en) * | 2010-07-16 | 2014-12-23 | The Trustees Of Columbia University In The City Of New York | Aldose reductase inhibitors and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2021130719A (ja) * | 2016-06-21 | 2021-09-09 | ザ トラスティーズ オブ コロンビア ユニバーシティー イン ザ シティー オブ ニューヨーク | アルドース還元酵素阻害剤およびその使用方法 |
| JP7368419B2 (ja) | 2016-06-21 | 2023-10-24 | ザ トラスティーズ オブ コロンビア ユニバーシティー イン ザ シティー オブ ニューヨーク | アルドース還元酵素阻害剤およびその使用方法 |
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